Microburst Electrical Stimulation Of Cranial Nerves For The Treatment Of Medical Conditions

ABSTRACT

Disclosed herein are methods, systems, and apparatus for treating a medical condition in a patient using an implantable medical device by applying an electrical signal characterized by having a number of pulses per microburst, an interpulse interval, a microburst duration, and an interburst period to a portion of a cranial nerve of said patient, wherein at least one of the number of pulses per microburst, the interpulse interval, the microburst duration, or the interburst period is selected to enhance cranial nerve evoked potentials.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of co-pending U.S. patent applicationSer. No. 12/400,970, filed Mar. 10, 2009, which is a continuation ofU.S. Pat. No. 8,615,309, filed Mar. 29, 2007, entitled “MicroburstElectrical Stimulation of Cranial Nerves for the Treatment of MedicalConditions,” which claims priority to U.S. Provisional PatentApplication No. 60/787,680, filed Mar. 29, 2006, entitled “SynchronizedAnd Optimized Vagus Nerve Stimulation Method,” which applications arehereby incorporated by reference herein in their entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to medical device systems and, moreparticularly, to medical device systems for applying electrical signalsto a cranial nerve for the treatment of various medical conditions, andfor improved electrical signals in such systems.

2. Description of the Related Art

Many advancements have been made in treating diseases such as depressionand epilepsy. Therapies using electrical signals for treating thesediseases have been found to effective. Implantable medical devices havebeen effectively used to deliver therapeutic stimulation to variousportions of the human body (e.g., the vagus nerve) for treating thesediseases. As used herein, “stimulation” or “stimulation signal” refersto the application of an electrical, mechanical, magnetic,electromagnetic, photonic, audio and/or chemical signal to a neuralstructure in the patient's body. The signal is an exogenous signal thatis distinct from the endogenous electrical, mechanical, and chemicalactivity (e.g., afferent and/or efferent electrical action potentials)generated by the patient's body and environment. In other words, thestimulation signal (whether electrical, mechanical, magnetic,electro-magnetic, photonic, audio or chemical in nature) applied to thenerve in the present invention is a signal applied from an artificialsource, e.g., a neurostimulator.

A “therapeutic signal” refers to a stimulation signal delivered to apatient's body with the intent of treating a medical condition byproviding a modulating effect to neural tissue. The effect of astimulation signal on neuronal activity is termed “modulation”; however,for simplicity, the terms “stimulating” and “modulating”, and variantsthereof, are sometimes used interchangeably herein. In general, however,the delivery of an exogenous signal itself refers to “stimulation” ofthe neural structure, while the effects of that signal, if any, on theelectrical activity of the neural structure are properly referred to as“modulation.” The modulating effect of the stimulation signal upon theneural tissue may be excitatory or inhibitory, and may potentiate acuteand/or long-term changes in neuronal activity. For example, the“modulating” effect of the stimulation signal to the neural tissue maycomprise one more of the following effects: (a) initiation of an actionpotential (afferent and/or efferent action potentials); (b) inhibitionor blocking of the conduction of action potentials, whether endogenousor exogenously induced, including hyperpolarizing and/or collisionblocking, (c) affecting changes in neurotransmitter/neuromodulatorrelease or uptake, and (d) changes in neuro-plasticity or neurogenesisof brain tissue.

In some embodiments, electrical neurostimulation may be provided byimplanting an electrical device underneath the skin of a patient anddelivering an electrical signal to a nerve such as a cranial nerve. Inone embodiment, the electrical neurostimulation involves sensing ordetecting a body parameter, with the electrical signal being deliveredin response to the sensed body parameter. This type of stimulation isgenerally referred to as “active,” “feedback,” or “triggered”stimulation. In another embodiment, the system may operate withoutsensing or detecting a body parameter once the patient has beendiagnosed with a medical condition that may be treated byneurostimulation. In this case, the system may apply a series ofelectrical pulses to the nerve (e.g., a cranial nerve such as a vagusnerve) periodically, intermittently, or continuously throughout the day,or over another predetermined time interval. This type of stimulation isgenerally referred to as “passive,” “non-feedback,” or “prophylactic,”stimulation. The electrical signal may be applied by an IMD that isimplanted within the patient's body. In another alternative embodiment,the signal may be generated by an external pulse generator outside thepatient's body, coupled by an RF or wireless link to an implantedelectrode.

Generally, neurostimulation signals that perform neuromodulation aredelivered by the IMD via one or more leads. The leads generallyterminate at their distal ends in one or more electrodes, and theelectrodes, in turn, are electrically coupled to tissue in the patient'sbody. For example, a number of electrodes may be attached to variouspoints of a nerve or other tissue inside a human body for delivery of aneurostimulation signal.

While feedback stimulation schemes have been proposed, conventionalvagus nerve stimulation (VNS) usually involves non-feedback stimulationcharacterized by a number of parameters. Specifically, conventionalvagus nerve stimulation usually involves a series of electrical pulsesin bursts defined by an “on-time” and an “off-time.” During the on-time,electrical pulses of a defined electrical current (e.g., 0.5-2.0milliamps) and pulse width (e.g., 0.25-1.0 milliseconds) are deliveredat a defined frequency (e.g., 20-30 Hz) for the on-time duration,usually a specific number of seconds, e.g., 10-60 seconds. The pulsebursts are separated from one another by the off-time, (e.g., 30seconds-5 minutes) in which no electrical signal is applied to thenerve. The on-time and off-time parameters together define a duty cycle,which is the ratio of the on-time to the combination of the on-time andoff-time, and which describes the percentage of time that the electricalsignal is applied to the nerve.

In conventional VNS, the on-time and off-time may be programmed todefine an intermittent pattern in which a repeating series of electricalpulse bursts are generated and applied to the vagus nerve 127. Eachsequence of pulses during an on-time may be referred to as a “pulseburst.” The burst is followed by the off-time period in which no signalsare applied to the nerve. The off-time is provided to allow the nerve torecover from the stimulation of the pulse burst, and to conserve power.If the off-time is set at zero, the electrical signal in conventionalVNS may provide continuous stimulation to the vagus nerve.Alternatively, the idle time may be as long as one day or more, in whichcase the pulse bursts are provided only once per day or at even longerintervals. Typically, however, the ratio of “off-time” to “on-time” mayrange from about 0.5 to about 10.

In addition to the on-time and off-time, the other parameters definingthe electrical signal in conventional VNS may be programmed over a rangeof values. The pulse width for the pulses in a pulse burst ofconventional VNS may be set to a value not greater than about 1 msec,such as about 250-500 μsec, and the number of pulses in a pulse burst istypically set by programming a frequency in a range of about 20-150 Hz(i.e., 20 pulses per second to 150 pulses per second). A non-uniformfrequency may also be used. Frequency may be altered during a pulseburst by either a frequency sweep from a low frequency to a highfrequency, or vice versa. Alternatively, the timing between adjacentindividual signals within a burst may be randomly changed such that twoadjacent signals may be generated at any frequency within a range offrequencies.

Although neurostimulation has proven effective in the treatment of anumber of medical conditions, it would be desirable to further enhanceand optimize neurostimulation for this purpose. For example, it may bedesirable to enhance evoked potentials in the patient's brain to aid intreating a medical condition.

SUMMARY OF THE INVENTION

Applicant has discovered that it is possible to provide improvedtherapeutic neurostimulation treatments for a variety of medicalconditions by a new type of electrical stimulation of the cranial nervescapable of providing enhanced evoked potentials in the brain. “Enhanced”in this context refers to electrical potentials evoked in the forebrainby neurostimulation that are higher than those produced by conventionalneurostimulation, particularly conventional VNS with an interpulsefrequency of 20-30 Hz (resulting in a number of pulses per burst of140-1800, at a burst duration from 7-60 sec). The electrical signal forthis improved therapy is substantially different from the electricalsignals in conventional VNS. In particular, electrical signals in thepresent invention are characterized by very short bursts of a limitednumber of electrical pulses. These shorts bursts of less than 1 secondare referred to hereinafter as “microbursts,” and electrical stimulationapplying microbursts to a cranial nerve is referred to as “microburststimulation.” By applying an electrical signal comprising a series ofmicrobursts to, for example, a vagus nerve of a patient, enhanced vagalevoked potentials (eVEP) are produced in therapeutically significantareas of the brain. Significantly, eVEP are not produced by conventionalvagus nerve stimulation.

As used herein, the term “microburst” refers to a portion of atherapeutic electrical signal comprising a limited plurality of pulsesand a limited duration. More particularly, in one embodiment, amicroburst may comprise at least two but no more than about 25electrical pulses, preferably from 2 to about 20 pulses per burst, morepreferably from 2 to about 15 pulses per burst. In one embodiment, amicroburst may last for no more than 1 second, typically less than 100milliseconds, and preferably from about 10 msec to about 80 msec. Atherapeutic electrical signal may comprise a series of microburstsseparated from one another by time intervals known as “interburstperiods” which allow a refractory interval for the nerve to recover fromthe microburst and again become receptive to eVEP stimulation by anothermicroburst. In some embodiments, the interburst period may be as long asor longer than the adjacent microbursts separated by the interburstperiod. In some embodiments the interburst period may comprise anabsolute time period of at least 100 milliseconds. Adjacent pulses in amicroburst are separated by a time interval known as an “interpulseinterval.” The interpulse interval, together with the number of pulsesand the pulse width of each pulse, determines a “microburst duration,”which is the length of a microburst from the beginning of the firstpulse to the end of the last pulse (and thus the beginning of a newinterburst period). In one embodiment, a microburst may have amicroburst duration of 1.0 seconds or less (i.e., not greater than 1sec), such as from about 2 msec to about 1 sec, and more preferably 100msec or less, such as from about 5 msec to about 100 msec, and morepreferably from about 10 msec to about 80 msec. The improved electricalsignals of the present invention are thus characterized by an interburstperiod, a microburst duration, a number of pulses per microburst, and aninterpulse interval. The pulses in a microburst may be furthercharacterized by a current amplitude and a pulse width. Electricalstimulation according to the present invention may optionally include anon-time and an off-time in which the microbursts are provided and notprovided, respectively, to a cranial nerve. At least one of theinterburst period, the burst duration, the number of pulses permicroburst, the interpulse interval, the current amplitude, the pulsewidth, the on-time, or the off-time can be selected to enhance cranialnerve evoked potentials.

In one embodiment, the present invention provides a method of treating apatient having a medical condition by applying a pulsed electricalsignal comprising a series of microbursts, wherein each of saidmicrobursts has at least one characteristic selected from the groupconsisting of having from 2 pulses to about 25 pulses per microburst,having an interpulse interval of about 1 millisecond to about 50milliseconds (such as from about 1 msec to about 10 msec), having amicroburst duration of less than 1 sec, and being separated from anadjacent microburst by an interburst period comprising a time intervalselected from the group consisting of A) the microburst duration or themicroburst duration of the adjacent microburst and B) at least 100milliseconds.

In one embodiment, the present invention provides a method of treating amedical condition of a patient with an electrical signal from animplantable medical device, comprising applying to a cranial nerve of apatient a pulsed electrical signal comprising a series of microburstsseparated by interburst periods. Each microburst comprises a number ofpulses per microburst, an interpulse interval, and a microburstduration. The microbursts are applied to a portion of a cranial nerve ofsaid patient, wherein at least one of the interburst period, themicroburst duration, the number of pulses per microburst, or theinterpulse interval is selected to enhance cranial nerve evokedpotentials.

In one embodiment, the present invention provides a method of treating amedical condition of a patient, comprising coupling at least oneelectrode to at least one cranial nerve of the patient, providing aprogrammable electrical signal generator coupled to the electrode, andgenerating a pulsed electrical signal comprising a series of microburstsseparated by interburst periods. Each microburst comprises a number ofpulses per microburst and an interpulse interval and has a microburstduration. The method further comprises selecting at least one of theinterburst period, the number of pulses per microburst, the microburstduration, or the interpulse interval to enhance cranial nerve evokedpotentials, and applying the pulsed electrical signal to the at leastone electrode to treat the medical condition.

In one embodiment, the present invention provides a computer readableprogram storage device encoded with instructions that, when executed bya computer, perform a method, comprising generating an electrical signalcomprising a series of microbursts separated by interburst periods, witheach microburst comprising a number of pulses per microburst, aninterpulse interval, and a microburst duration, wherein at least one ofthe interburst period, the number of pulses per microburst, themicroburst duration, or the interpulse period is selected to enhancecranial nerve evoked potentials, and applying the electrical signal to acranial nerve of the patient to treat the medical condition.

In one embodiment, the present invention provides a system for treatinga medical condition of a patient, comprising at least one electrodecoupled to at least one cranial nerve of a patient and an implantabledevice operatively coupled to the electrode and comprising an electricalsignal generator capable of generating an electrical signal comprising aseries of microbursts separated by interburst periods, with eachmicroburst comprising a number of pulses per microburst, an interpulseinterval and a microburst duration, and applying the electrical signalto a portion of a cranial nerve of said patient using the electrode,wherein at least one of the interburst period, the number of pulses permicroburst, the interpulse interval or the microburst duration, isselected to enhance cranial nerve evoked potentials.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be understood by reference to the followingdescription taken in conjunction with the accompanying drawings, inwhich like reference numerals identify like elements, and in which:

FIG. 1 provides a stylized diagram of an implantable medical deviceimplanted into a patient's body for providing a therapeutic electricalsignal to a neural structure of the patient's body, in accordance withone illustrative embodiment of the present invention;

FIG. 2 is a block diagram of a medical device system that includes animplantable medical device and an external device, in accordance withone illustrative embodiment of the present invention;

FIG. 3 illustrates an exemplary electrical signal of a firing neuron asa graph of voltage at a given location at particular times in responseto application of an electrical signal to the nerve by theneurostimulator of FIG. 2, in accordance with one illustrativeembodiment of the present invention;

FIGS. 4A, 4B, and 4C illustrate exemplary waveforms for electricalsignals for stimulating the cranial nerve for treating a medicalcondition, according to one illustrative embodiment of the presentinvention;

FIG. 5 illustrates a flowchart depiction of a method for treating amedical condition, in accordance with an illustrative embodiment of thepresent invention;

FIG. 6 illustrates a flowchart depiction of an alternative method fortreating a medical condition, in accordance with an alternativeillustrative embodiment of the present invention;

FIG. 7 depicts a more detailed flowchart depiction of the step ofperforming a detection process of FIG. 6, in accordance with anillustrative embodiment of the present invention;

FIGS. 8A-8E show a comparison of vagal evoked potentials (VEPs) withdifferent stimulus timings;

FIG. 9 illustrates synchronization of a vagal stimulus burst to the QRSwave of a patient's ECG;

FIG. 10 illustrates the localization of an early VEP in the rightthalamus and basal ganglia and a later VEP in the left insular cortex.

While the invention is susceptible to various modifications andalternative forms, specific embodiments thereof have been shown by wayof example in the drawings and are herein described in detail. It shouldbe understood, however, that the description herein of specificembodiments is not intended to limit the invention to the particularforms disclosed, but on the contrary, the intention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Illustrative embodiments of the invention are described herein. In theinterest of clarity, not all features of an actual implementation aredescribed in this specification. In the development of any such actualembodiment, numerous implementation-specific decisions must be made toachieve the design-specific goals, which will vary from oneimplementation to another. It will be appreciated that such adevelopment effort, while possibly complex and time-consuming, wouldnevertheless be a routine undertaking for persons of ordinary skill inthe art having the benefit of this disclosure.

This document does not intend to distinguish between components thatdiffer in name but not function. In the following discussion and in theclaims, the terms “including” and “includes” are used in an open-endedfashion, and thus should be interpreted to mean “including, but notlimited to.” Also, the term “couple” or “couples” is intended to meaneither a direct or an indirect electrical connection. “Direct contact,”“direct attachment,” or providing a “direct coupling” indicates that asurface of a first element contacts the surface of a second element withno substantial attenuating medium there between. The presence of smallquantities of substances, such as bodily fluids, that do notsubstantially attenuate electrical connections does not vitiate directcontact. The word “or” is used in the inclusive sense (i.e., “and/or”)unless a specific use to the contrary is explicitly stated.

The term “electrode” or “electrodes” described herein may refer to oneor more stimulation electrodes (i.e., electrodes for delivering anelectrical signal generated by an IMD to a tissue), sensing electrodes(i.e., electrodes for sensing a physiological indication of a patient'sbody), and/or electrodes that are capable of delivering a stimulationsignal, as well as performing a sensing function.

Cranial nerve stimulation has been proposed to treat a number of medicalconditions pertaining to or mediated by one or more structures of thenervous system of the body, including epilepsy and other movementdisorders, depression, anxiety disorders and other neuropsychiatricdisorders, dementia, head trauma, coma, migraine headache, obesity,eating disorders, sleep disorders, cardiac disorders (such as congestiveheart failure and atrial fibrillation), hypertension, endocrinedisorders (such as diabetes and hypoglycemia), and pain, among others.See, e.g., U.S. Pat. Nos. 4,867,164; 5,299,569; 5,269,303; 5,571,150;5,215,086; 5,188,104; 5,263,480; 6,587,719; 6,609,025; 5,335,657;6,622,041; 5,916,239; 5,707,400; 5,231,988; and 5,330,515. Despite thenumerous disorders for which cranial nerve stimulation has been proposedor suggested as a treatment option, the fact that detailed neuralpathways for many (if not all) cranial nerves remain relatively unknown,makes predictions of efficacy for any given disorder difficult orimpossible. Moreover, even if such pathways were known, the precisestimulation parameters that would modulate particular pathways relevantto a particular disorder generally cannot be predicted.

In one embodiment, the present invention provides a method of treating amedical condition. The medical condition can be selected from the groupconsisting of epilepsy, neuropsychiatric disorders (including but notlimited to depression), eating disorders/obesity, traumatic braininjury/coma, addiction disorders, dementia, sleep disorders, pain,migraine, endocrine/pancreatic disorders (including but not limited todiabetes), motility disorders, hypertension, congestive heartfailure/cardiac capillary growth, hearing disorders, angina, syncope,vocal cord disorders, thyroid disorders, pulmonary disorders, andreproductive endocrine disorders (including infertility).

In one embodiment, the present invention provides a method of treating amedical condition of a patient using an implantable medical device,comprising applying to a cranial nerve of a patient a pulsed electricalsignal comprising a series of microbursts separated by interburstperiods. In one embodiment, the interburst periods comprise at least 100milliseconds each. In another embodiment, the interburst periodscomprise at least the length of one of the two microbursts separated bythe interburst period. In another embodiment, the interburst period maybe determined on a particular patient by providing microbursts separatedby increasingly smaller interburst periods. The interburst period may beprovided as any time interval greater than that at which the eVEPsignificantly diminishes or disappear. Each microburst comprises anumber of pulses per microburst, an interpulse interval, and has amicroburst duration. In one embodiment, the number of pulses permicroburst may range from 2 to about 25 pulses, and in anotherembodiment the number pulses per microburst may range from 2 to about 20pulses, preferably from 2 to about 15 pulses. The microbursts areapplied to a portion of a cranial nerve of the patient, and at least oneof the interburst period, the number of pulses per microburst, theinterpulse interval, or the microburst duration are selected to enhancecranial nerve evoked potentials. Pulses within a microburst may alsocomprise a pulse width and a current amplitude. In an alternateembodiment, the method may also comprise an off-time, during whichmicrobursts are not applied to the patient, and an on-time during whichmicrobursts are applied to the patient.

It may be convenient to refer to a burst frequency, defined as 1 dividedby the sum of the microburst duration and the interburst period, and itwill be recognized by persons of skill in the art that the interburstperiod may alternatively be described in terms of a frequency of thepulses rather than as an absolute time separate one pulse from another.

In another alternate embodiment, the method may comprise, during a firstperiod, applying a primary mode of cranial nerve stimulation to acranial nerve of the patient, such as conventional vagus nervestimulation, and, during a second period, applying a secondary mode ofcranial nerve stimulation to a cranial nerve of the patient, such asmicroburst stimulation. The conventional vagus nerve stimulation signalmay be defined by a current amplitude, a pulse width, a frequency, anon-time and an off-time. The conventional vagus nerve stimulation signaltypically has more than about 50 pulses per burst and a burst durationof at least about 7 sec. In one embodiment, the first period correspondsto the on-time of conventional vagus nerve stimulation and the secondtime period corresponds to the off-time of conventional vagus nervestimulation. In another embodiment, the first period and the secondperiod can partially overlap. In another embodiment, one of the firstperiod or the second period can be entirely overlapped by the other ofthe first period or the second period.

The implantable medical device (IMD) system of one embodiment of thepresent invention provides for software module(s) that are capable ofacquiring, storing, and processing various forms of data, such aspatient data/parameters (e.g., physiological data, side-effects data,such as heart rate, breathing rate, brain-activity parameters, diseaseprogression or regression data, quality of life data, etc.) and therapyparameter data. Therapy parameters may include, but are not limited to,electrical signal parameters that define the therapeutic electricalsignals delivered by the IMD, medication parameters and/or any othertherapeutic treatment parameter. In an alternative embodiment, the term“therapy parameters” may refer to electrical signal parameters definingthe therapeutic electrical signals delivered by the IMD. Therapyparameters for a therapeutic electrical signal may also include, but arenot limited to, a current amplitude, a pulse width, an interburstperiod, a number of pulses per burst, an interpulse interval, a burstduration, an on-time, and an off-time.

Although not so limited, a system capable of implementing embodiments ofthe present invention is described below. FIG. 1 depicts a stylizedimplantable medical system (IMD) 100 for implementing one or moreembodiments of the present invention. An electrical signal generator 110is provided, having a main body 112 comprising a case or shell with aheader 116 for connecting to an insulated, electrically conductive leadassembly 122. The generator 110 is implanted in the patient's chest in apocket or cavity formed by the implanting surgeon just below the skin(indicated by a dotted line 145), similar to the implantation procedurefor a pacemaker pulse generator.

A nerve electrode assembly 125, preferably comprising a plurality ofelectrodes having at least an electrode pair, is conductively connectedto the distal end of the lead assembly 122, which preferably comprises aplurality of lead wires (one wire for each electrode). Each electrode inthe electrode assembly 125 may operate independently or alternatively,may operate in conjunction with the other electrodes. In one embodiment,the electrode assembly 125 comprises at least a cathode and an anode. Inanother embodiment, the electrode assembly comprises one or moreunipolar electrodes.

Lead assembly 122 is attached at its proximal end to connectors on theheader 116 of generator 110. The electrode assembly 125 may besurgically coupled to the vagus nerve 127 in the patient's neck or atanother location, e.g., near the patient's diaphragm or at theesophagus/stomach junction. Other (or additional) cranial nerves such asthe trigeminal and/or glossopharyngeal nerves may also be used todeliver the electrical signal in particular alternative embodiments. Inone embodiment, the electrode assembly 125 comprises a bipolarstimulating electrode pair 126, 128 (i.e., a cathode and an anode).Suitable electrode assemblies are available from Cyberonics, Inc.,Houston, Tex., USA as the Model 302 electrode assembly. However, personsof skill in the art will appreciate that many electrode designs could beused in the present invention. In one embodiment, the two electrodes arewrapped about the vagus nerve, and the electrode assembly 125 may besecured to the vagus nerve 127 by a spiral anchoring tether 130 such asthat disclosed in U.S. Pat. No. 4,979,511 issued Dec. 25, 1990 to ReeseS. Terry, Jr. and assigned to the same assignee as the instantapplication. Lead assembly 122 may be secured, while retaining theability to flex with movement of the chest and neck, by a sutureconnection to nearby tissue (not shown).

In alternative embodiments, the electrode assembly 125 may comprisetemperature sensing elements and/or heart rate sensor elements. Othersensors for other body parameters may also be employed to trigger activestimulation. Both passive and active stimulation may be combined ordelivered by a single IMD according to the present invention. Either orboth modes may be appropriate to treat a specific patient underobservation.

In alternative embodiments, a sensor assembly 165, comprising a sensorlead assembly 162 and a sensor 160, may be employed to detect a bodyparameter of the patient.

The electrical pulse generator 110 may be programmed with an externaldevice (ED) such as computer 150 using programming software known in theart. A programming wand 155 may be coupled to the computer 150 as partof the ED to facilitate radio frequency (RF) communication between thecomputer 150 and the pulse generator 110. The programming wand 155 andcomputer 150 permit non-invasive communication with the generator 110after the latter is implanted. In systems where the computer 150 usesone or more channels in the Medical Implant Communications Service(MICS) bandwidths, the programming wand 155 may be omitted to permitmore convenient communication directly between the computer 150 and thepulse generator 110.

The therapeutic electrical stimulation signal described herein may beused to treat a medical condition by enhancing cranial nerve evokedpotentials separately, or in combination with another type of treatment.For example, electrical signals according to the present invention maybe applied in combination with a chemical agent, such as various drugs,to treat various medical conditions. Further, the electrical stimulationmay be performed in combination with treatment(s) relating to abiological or chemical agent. The electrical stimulation treatment mayalso be performed in combination with other types of treatment, such asmagnetic stimulation treatment.

Turning now to FIG. 2, a block diagram depiction of the IMD 200 isprovided, in accordance with one illustrative embodiment of the presentinvention. The IMD 200 (such as generator 110 from FIG. 1) may comprisea controller 210 capable of controlling various aspects of the operationof the IMD 200. The controller 210 is capable of receiving internal dataor external data and causing a stimulation unit 220 to generate anddeliver an electrical signal to target tissues of the patient's body fortreating a medical condition. For example, the controller 210 mayreceive manual instructions from an operator externally, or may causethe electrical signal to be generated and delivered based on internalcalculations and programming. The controller 210 is capable of affectingsubstantially all functions of the IMD 200.

The controller 210 may comprise various components, such as a processor215, a memory 217, etc. The processor 215 may comprise one or moremicrocontrollers, microprocessors, etc., capable of performing variousexecutions of software components. The memory 217 may comprise variousmemory portions where a number of types of data (e.g., internal data,external data instructions, software codes, status data, diagnosticdata, etc.) may be stored. The memory 217 may comprise one or more ofrandom access memory (RAM) dynamic random access memory (DRAM),electrically erasable programmable read-only memory (EEPROM), flashmemory, etc.

The IMD 200 may also comprise a stimulation unit 220 capable ofgenerating and delivering electrical signals to one or more electrodesvia leads. A lead assembly such as lead assembly 122 (FIG. 1) may becoupled to the IMD 200. Therapy may be delivered to the leads comprisingthe lead assembly 122 by the stimulation unit 220 based uponinstructions from the controller 210. The stimulation unit 220 maycomprise various circuitry, such as electrical signal generators,impedance control circuitry to control the impedance “seen” by theleads, and other circuitry that receives instructions relating to thedelivery of the electrical signal to tissue. The stimulation unit 220 iscapable of delivering an electrical signal over the leads comprising thelead assembly 122.

The IMD 200 may also comprise a power supply 230. The power supply 230may comprise a battery, voltage regulators, capacitors, etc., to providepower for the operation of the IMD 200, including delivering thetherapeutic electrical signal. The power supply 230 comprises a powersource that in some embodiments may be rechargeable. In otherembodiments, a non-rechargeable power source may be used. The powersupply 230 provides power for the operation of the IMD 200, includingelectronic operations and the electrical signal generation and deliveryfunctions. The power supply 230 may comprise a lithium/thionyl chloridecell or a lithium/carbon monofluoride (LiCF_(x)) cell. Other batterytypes known in the art of implantable medical devices may also be used.

The IMD 200 may also comprise a communication unit 260 capable offacilitating communications between the IMD 200 and various devices. Inparticular, the communication unit 260 is capable of providingtransmission and reception of electronic signals to and from an externalunit 270, such as computer 150 and wand 155 that may comprise an ED(FIG. 1). The communication unit 260 may include hardware, software,firmware, or any combination thereof.

In one embodiment, the IMD 200 may also comprise a detection unit 295that is capable of detecting various patient parameters. For example,the detection unit 295 may comprise hardware, software, or firmware thatis capable of obtaining and/or analyzing data relating to one or morebody parameters of the patient. Based upon the data obtained by thedetection unit 295, the IMD 200 may deliver the electrical signal to aportion of the cranial nerve to treat epilepsy, depression or othermedical conditions. In one embodiment, the detection unit 295 may becapable of detecting a feedback response from the patient. The feedbackresponse may include a magnetic signal input, a tap input, a wirelessdata input to the MID 200, etc. The feedback may be indicative of a painand/or noxious threshold, wherein the threshold may be the limit oftolerance of discomfort for a particular patient. The term “patientparameters” may refer to, but is not limited to, various bodyparameters, which may in some embodiments involve sensors coupled to theIMD 200.

In another embodiment, the detection unit 295 may comprise hardware,software, or firmware that is capable of obtaining and/or analyzing datarelating to one or more body parameters of the patient's cardiac cycle.Based upon the data obtained by the detection unit 295, the IMD 200 maydeliver the electrical signal to a portion of the cranial nerve to treatepilepsy, depression or other medical conditions.

The external unit 270 may be an ED that is capable of programmingelectrical signal parameters of the IMD 200. In one embodiment, theexternal unit 270 is a computer system capable of executing adata-acquisition program. The external unit 270 may be controlled by ahealthcare provider, such as a physician, at a base station in, forexample, a doctor's office. In alternative embodiments, the externalunit 270 may be controlled by a patient in a system providing lesscontrol over the operation of the IMD 200 than another external unit 270controlled by a healthcare provider. Whether controlled by the patientor by a healthcare provider, the external unit 270 may be a computer,preferably a handheld computer or PDA, but may alternatively compriseany other device that is capable of electronic communications andprogramming, e.g., hand-held computer system, a PC computer system, alaptop computer system, a server, a personal digital assistant (PDA), anApple-based computer system, etc. The external unit 270 may downloadvarious parameters and program software into the MD 200 for programmingthe operation of the IMD, and may also receive and upload various statusconditions and other data from the IMD 200. Communications between theexternal unit 270 and the communication unit 260 in the IMD 200 mayoccur via a wireless or other type of communication, representedgenerally by line 277 in FIG. 2. This may occur using, e.g., wand 155(FIG. 1) to communicate by RF energy with a generator 110.Alternatively, the wand may be omitted in some systems, e.g., systems inwhich external unit 270 operates in the MICS bandwidths.

In one embodiment, the external unit 270 may comprise a local databaseunit 255. Optionally or alternatively, the external unit 270 may also becoupled to a database unit 250, which may be separate from external unit270 (e.g., a centralized database wirelessly linked to a handheldexternal unit 270). The database unit 250 and/or the local database unit255 are capable of storing various patient data. This data may comprisepatient parameter data acquired from a patient's body and/or therapyparameter data. The database unit 250 and/or the local database unit 255may comprise data for a plurality of patients, and may be organized andstored in a variety of manners, such as in date format, severity ofdisease format, etc. The database unit 250 and/or the local databaseunit 255 may be relational databases in one embodiment. A physician mayperform various patient management functions using the external unit270, which may include obtaining and/or analyzing data from the IMD 200and/or data from the database unit 250 and/or the local database unit255. The database unit 250 and/or the local database unit 255 may storevarious patient data.

One or more of the blocks illustrated in the block diagram of the IMD200 in FIG. 2, may comprise hardware units, software units, firmwareunits, or any combination thereof. Additionally, one or more blocksillustrated in FIG. 2 may be combined with other blocks, which mayrepresent circuit hardware units, software algorithms, etc.Additionally, any number of the circuitry or software units associatedwith the various blocks illustrated in FIG. 2 may be combined into aprogrammable device, such as a field programmable gate array, an ASICdevice, etc.

FIG. 3 provides a stylized depiction of an exemplary electrical signalof a firing neuron as a graph of voltage at a given point on the nerveat particular times during the propagation of an action potential alongthe nerve, in accordance with one embodiment of the present invention. Atypical neuron has a resting membrane potential of about −70 mV,maintained by transmembrane ion channel proteins. When a portion of theneuron reaches a firing threshold of about −55 mV, the ion channelproteins in the locality allow the rapid ingress of extracellular sodiumions, which depolarizes the membrane to about +30 mV. The wave ofdepolarization then propagates along the neuron. After depolarization ata given location, potassium ion channels open to allow intracellularpotassium ions to exit the cell, lowering the membrane potential toabout −80 mV (hyperpolarization). About 1 msec is required fortransmembrane proteins to return sodium and potassium ions to theirstarting intra- and extracellular concentrations and allow a subsequentaction potential to occur.

Referring again to FIG. 1, the IMD 100 may generate a pulsed electricalsignal in embodiments of the present invention for application to acranial nerve such as vagus nerve 127 according to one or moreprogrammed parameters. In one embodiment, the parameters defining theelectrical signal may be selected from the group consisting of aninterburst period, a number of pulses per burst, an interpulse interval,a burst duration, a current magnitude, a pulse width, an on-time, and anoff-time. Suitable ranges for these parameters may comprise a variety ofvalues. In particular, the interburst period in microburst signalsaccording to the present invention may, in one embodiment, be 100milliseconds or greater, preferably 100 milliseconds to 10 minutes, andmore preferably 1 second to 5 seconds. In another embodiment, theinterburst period may be equal to or greater than the microburstduration of one of the two adjacent microbursts that the interburstperiod separates. The number of pulses comprising a microburst may rangefrom about 2 to about 25 pulses, such as from 2 to about 20 pulses, andmore specifically from 2 to about 15 pulses. Suitable interpulseintervals in the present invention may range from about 1 millisecond toabout 50 milliseconds, more preferably from about 2 milliseconds toabout 10 milliseconds. Suitable microburst durations may range fromabout 2 msec to about 1 sec, preferably less than about 100 msec, morepreferably from about 5 msec to about 100 msec, and even more preferablyfrom about 10 msec to about 80 msec.

Ranges for current magnitude and pulse width may comprise values similarto those for conventional VNS signals, e.g., current magnitudes of0.10-6.0 milliamps, preferably 0.25-3.0 milliamps, and more preferably0.5-2.0 milliamps. Pulse widths may range from about 0.05 to about 1.0milliseconds, preferably 0.25 to about 0.5 milliseconds. In view of thestated values of pulse width and interpulse intervals, a 2-pulsemicroburst could comprise a microburst duration of as little as 1.1milliseconds, while a microburst of 25 pulses could last as long asabout 1275 milliseconds, although microburst durations of 100milliseconds or less are preferred. In embodiments of the presentinvention, however, the microbursts are no greater than 1 second induration.

In one embodiment, microburst signals of the present invention may beapplied to the nerve continuously, with microbursts being applied to thenerve separated only by the interburst period (e.g., 1 to 5 seconds in apreferred embodiment). In an alternative embodiment, the concepts of“on-time” and “off-time” associated with conventional VNS therapy may beused to provide an on-time interval in which microbursts, separated bythe interburst period, are applied to the nerve for the duration of theon-time, followed by an off-time period in which no electrical signal isapplied to the nerve. Thus, for example, a series of microburstsseparated by an interburst period of 1 second, in which each microburstcomprises 3 pulses separated by an interpulse interval of 5 msec, may beapplied to a vagus nerve of the patient for an on-time of 5 minutes,followed by an off-time of 10 minutes in which no electrical signal isapplied to the nerve. In some embodiments, the on-time may range fromabout 100 msec to about 60 minutes. In such embodiments, the off-timesmay range from 200 msec to 24 hours or more.

In a further embodiment, during the off-time of the microburststimulation, an alternative stimulation technique, such as conventionalcranial nerve stimulation, can be performed. Conventional cranial nervestimulation generally also involves an on-time and an off-time, and theon-time of the microburst stimulation may be during the off-time of theconventional cranial nerve stimulation.

If both microburst stimulation and an alternative stimulation techniqueare performed, the on-times, the off-times, or both of the twostimulation regimes may partially or wholly overlap.

Exemplary pulse waveforms in accordance with one embodiment of thepresent invention are shown in FIGS. 4A-4C. Pulse shapes in electricalsignals according to the present invention may include a variety ofshapes known in the art including square waves, biphasic pulses(including active and passive charge-balanced biphasic pulses),triphasic waveforms, etc. In one embodiment, the pulses comprise asquare, biphasic waveform in which the second phase is acharge-balancing phase of the opposite polarity to the first phase.

In microburst stimulation according to the present invention, themicrobursts are markedly shorter in both the number of pulses and themicroburst duration compared to pulse bursts in conventionalneurostimulation such as vagus nerve stimulation. While conventional VNStypically involves pulse bursts at a frequency of 20-30 Hz for a periodof from 7-60 seconds (resulting in a burst having from 140-1800 pulsesor more), microbursts according to the present invention, by contrast,can have a microburst duration from about 1 msec to no more than 1second. Further, each microburst comprises at least 2 and about 25pulses, with each of the pulses separated from an adjacent pulse by aninterpulse interval of from about 1 to about 50 milliseconds, moretypically from about 2 to about 10 milliseconds. While the individualpulses in a microburst according to this aspect of the invention mayresemble conventional VNS signal pulses in pulse width and pulsecurrent, the number of pulses in a microburst is markedly smaller thanin a pulse burst in conventional VNS therapy. Consequently, microburstsare also much shorter in duration (less than 1 second and typically lessthan 100 msec, such as from about 10 msec to about 80 msec) than pulsebursts in conventional neurostimulation therapy (at least 7 seconds andtypically 20-60 seconds). Moreover, in most cases, the interpulseinterval separating the pulses is shorter than in conventionalneurostimulation (typically 2-10 msec for microbursts compared to 30-50msec for conventional VNS). Pulse bursts of the present invention aretermed “microbursts” because they are significantly shorter in both thenumber of pulses and the total microburst duration than conventionalneurostimulation signals.

As noted, it has been discovered by the present inventor thatmicrobursts according to this aspect of the invention are capable ofproviding an enhanced vagal evoked potential (eVEP) in the patient'sbrain that is significantly greater than VEPs produced by conventionalvagus nerve stimulation signals. This eVEP is attenuated, however, asthe number of pulses increases beyond an optimal number of pulses. Thus,for example, in the monkey model discussed below, where a microburstexceeds 2-5 pulses, the eVEP begins to diminish, and if more than 15pulses are provided, the eVEP is highly diminished. To maintain the eVEPeffect, this aspect of the present invention requires a small number ofpulses in a microburst as well as an interburst period separating eachmicroburst from the adjacent microburst in order to allow the nerve arefractory space to recover from the microburst. Providing anappropriate interburst period ensures that the succeeding microburst inthe electrical signal is capable of generating an eVEP. In oneembodiment the interburst period is as long as or longer than theduration of the adjacent microbursts separated by the interburst period.In another embodiment, the interburst period is at least 100milliseconds, such as from about 1 sec to about 5 sec. Each microburstcomprises a series of pulses that, in some embodiments, are intended tomimic the endogenous afferent activity on the vagus nerve. In oneembodiment the microbursts may simulate afferent vagal action potentialsassociated with each cardiac and respiratory cycle.

Although evoked potentials have been discussed above in the context ofthe vagus nerve, enhanced evoked potentials can be generated bymicroburst stimulation of any cranial nerve, e.g. the trigeminal nerveor glossopharyngeal nerve, and remain within the spirit and scope of thepresent invention. Thus, while the present invention is presented, incertain embodiments, as providing microburst stimulation to a vagusnerve of a patient, microburst stimulation may also be applied to othercranial nerves, and particularly the trigeminal nerve and theglossopharyngeal nerve.

The central vagal afferent pathways involve two or more synapses beforeproducing activity in the forebrain. Each synaptic transfer is apotential site of facilitation and a nonlinear temporal filter, forwhich the sequence of interpulse intervals in a microburst can beoptimized. Without being bound by theory, it is believed that the use ofmicrobursts enhances VNS efficacy by augmenting synaptic facilitationand “tuning” the input stimulus train to maximize the forebrain evokedpotential.

For example, as shown in FIG. 8, the vagal evoked potential (VEP)measured in the monkey thalamus is barely visible if elicited by asingle stimulus pulse on the vagus nerve (FIG. 8A) and it virtuallydisappears if the single stimuli are presented in a train at 30 Hz, asin conventional neurostimulation (FIG. 8B). However, as shown in theseries of traces in the middle and lower panels of the figure, the VEPis enormously enhanced (resulting in eVEP) and optimized by using amicroburst of pulses (2-6 pulses, microburst duration ltoreq.1 second,FIG. 8C) at appropriate interpulse intervals (in this case, 6.7 msec wasoptimal for the first interpulse interval, shown in FIG. 8D) and at aninterburst period (i.e., burst frequency) that approximates theelectrocardiogram R-R cycle (the period between R-waves of consecutiveheartbeats) in the monkey (in this case 0.3 Hz, shown as FIG. 8E).

The use of pairs of pulses is a standard physiological tool forproducing central responses by stimulation of small-diameter afferentfibers. However, according to the present disclosure, a microburst withan appropriate sequence of interpulse intervals enormously enhances theeffect of neurostimulation. By selecting an appropriate interburstperiod, an electrical signal for neurostimulation may comprise a seriesof microbursts that each provide eVEP. As illustrated in FIG. 8, amicroburst duration of >10 msec produces a maximal VEP in the monkey anda first interpulse interval of .about.6-9 msec produces maximalfacilitation, and so according to the present disclosure, a microburstof pulses with a total duration of about 10-20 msec and with aninterpulse interval of about 6-9 msec and subsequent microbursts ofsimilar duration will produce an optimal VEP in the monkey model. Thoughnot to be bound by theory, the eVEP may result because such a microburstsimulates the pattern of action potentials that occur naturally in thesmall-diameter afferent vagal fibers that elicit the central responsethat the present enhanced and optimized therapy may evoke (see below).Selection of an appropriate interburst period to separate one microburstfrom the next may be performed experimentally, although as previouslynoted, a refractory period of at least 100 msec (such as from 100 msecto 10 min, such as 1 sec to 5 sec) and at least equal to the microburstduration is most desired.

The sequence of interpulse intervals may vary with the patient's heartrate variability (HRV) (reflecting cardiac and respiratory timing) andalso between individual patients, and thus, in one embodiment, thenumber of pulses, on-time duration, off-time duration, microburstfrequency, the interpulse interval, the interburst period, and themicroburst duration may be optimized for each patient. As a standardmicroburst sequence for initial usage, a microburst of 2 or 3 pulses atinterpulse intervals of 5-10 msec will approximate the short peak ofendogenous post-cardiac activity. The interburst period may also bedetermined empirically by providing microbursts with a steadilydecreasing interburst period until the eVEP begins to decline. In oneembodiment, the interpulse interval is a series of equal intervals(i.e., the simplest train) or increasing intervals, simulating thepattern of a decelerating post-synaptic potential, as illustrated inFIG. 9. In an alternative embodiment, the interpulse intervals maydecrease through the microburst, or may be randomly determined within apreselected range, e.g., 5-20 msec. This modification of conventionalneurostimulation methodology may produce a significant enhancement ofneurostimulation efficacy that is applicable to many different medicalconditions.

The optimization may be accomplished by recording, using surfaceelectrodes, a far-field VEP, which originates from the thalamus andother regions of the forebrain, and varying the stimulus parameters inorder to maximize the recorded potential. As illustrated in FIG. 1,standard EEG recording equipment 194 and 16- or 25-lead electrodeplacement (of which five electrodes 190 are shown, with leads 192 inelectrical communication with the EEG recording equipment 194), such astypically used clinically for recording somatosensory or auditory evokedpotentials, will enable the VEP to be recorded and identified as an EEGrecording 198. Neurostimulation stimulus burst timing can be used tosynchronize averages of 8 to 12 epochs, if desired. By testing theeffects of varied numbers of pulses, interpulse intervals, microburstdurations, and interburst periods in defining the microbursts, thepeak-to-peak amplitude of the eVFP in a microburst can be optimized ineach patient.

Neurostimulation can be optimized in individual patients by selectedstimulus parameters that produce the greatest effect as measured withEEG surface electrodes. The current amplitude and pulse width is firstoptimized by measuring the size of the VEP elicited by individual pulses(as opposed to a microburst). The number of pulses, interpulseintervals, microburst durations, and interburst periods for themicrobursts are then optimized using the current amplitude and pulsewidth previously determined, by measuring the size of the eVEP inducedby the microbursts.

Because the large eVEPs recorded in the thalamus, striatum, and insularcortex of the anesthetized monkey shown in FIG. 8, are large enough thatif evoked in a human patient, the eVEPs are observable in a standard EEGdetected using electrodes adjacent to the human patient's scalp, thestandard EEG may be used to indicate the effects of modifications to thesignal parameters of the exogenous electrical signal. In this manner,the EEG may be used to optimize or tune the neurostimulation electricalsignal parameters for microbursts empirically. Without being bound bytheory, it is believed that the eVEP recorded in the right thalamus andstriatum is significant for the anti-epileptic effects ofneurostimulation, whereas another potential (in the left insular cortex)is most significant for the anti-depression effects of neurostimulation.By using regional EEG localization on the right or left frontalelectrodes (FIG. 10), the neurostimulation electrical signal parametersfor microbursts according to this aspect of the invention can beoptimized appropriately by measuring the eVEP in these respectiveregions for individual patients.

The optimal microburst parameters for eliciting eVEPs from these twoareas (right thalamus/striatum and left insular cortex, respectively)may differ. Both eVEPs are identifiable with EEG recording methods inawake human patients, so that the appropriate area may easily be usedfor parametric optimization in an epilepsy or depression patient.

The regional EEG localization represented in FIG. 10 allows the earlyVEP in the right thalamus and basal ganglia associated with theantiepileptic effects of neurostimulation to be distinguished from thelater VEP in the left thalamus and insular cortex that may be associatedwith the treatment of other medical conditions.

In one embodiment, the present invention may include coupling of atleast one electrode to each of two or more cranial nerves. (In thiscontext, two or more cranial nerves mean two or more nerves havingdifferent names or numerical designations, and do not refer to the leftand right versions of a particular nerve). In one embodiment, at leastone electrode may be coupled to either or both vagus nerves or a branchof either or both vagus nerves. The term “operatively” coupled mayinclude directly or indirectly coupling. Each of the nerves in thisembodiment or others involving two or more cranial nerves may bestimulated according to particular activation modalities that may beindependent between the two nerves.

Another activation modality for stimulation is to program the output ofthe IMD 100 to the maximum amplitude which the patient may tolerate. Thestimulation may be cycled on and off for a predetermined period of timefollowed by a relatively long interval without stimulation. Where thecranial nerve stimulation system is completely external to the patient'sbody, higher current amplitudes may be needed to overcome theattenuation resulting from the absence of direct contact with thecranial nerve, such as vagus nerve 127, and the additional impedance ofthe skin of the patient. Although external systems typically requiregreater power consumption than implantable ones, they have an advantagein that their batteries may be replaced without surgery.

Returning to systems for providing cranial nerve stimulation, such asthat shown in FIGS. 1 and 2, stimulation may be provided in at least twodifferent modalities. Where cranial nerve stimulation is provided basedsolely on programmed off-times and on-times, the stimulation may bereferred to as passive, inactive, or non-feedback stimulation. Incontrast, stimulation may be triggered by one or more feedback loopsaccording to changes in the body or mind of the patient. Thisstimulation may be referred to as active or feedback-loop stimulation.In one embodiment, feedback-loop stimulation may be manually-triggeredstimulation, in which the patient manually causes the activation of apulse burst outside of the programmed on-time/off-time cycle. Thepatient may manually activate the IMD 100 to stimulate the cranialnerve, such as vagus nerve 127, to treat an acute episode of a medicalcondition. The patient may also be permitted to alter the intensity ofthe signals applied to the cranial nerve within limits established bythe physician.

Patient activation of an IMD 100 may involve use of an external controlmagnet for operating a reed switch in an implanted device, for example.Certain other techniques of manual and automatic activation ofimplantable medical devices are disclosed in U.S. Pat. No. 5,304,206 toBaker, Jr., et al., assigned to the same assignee as the presentapplication (“the '206 patent”). According to the '206 patent, means formanually activating or deactivating the electrical signal generator 110may include a sensor such as piezoelectric element mounted to the innersurface of the generator case and adapted to detect light taps by thepatient on the implant site. One or more taps applied in fast sequenceto the skin above the location of the electrical signal generator 110 inthe patient's body may be programmed into the implanted medical device100 as a signal for activation of the electrical signal generator 110.Two taps spaced apart by a slightly longer duration of time may beprogrammed into the IMD 100 to indicate a desire to deactivate theelectrical signal generator 110, for example. The patient may be givenlimited control over operation of the device to an extent which may bedetermined by the program dictated or entered by the attendingphysician. The patient may also activate the IMD 100 using othersuitable techniques or apparatus.

In some embodiments, feedback stimulation systems other thanmanually-initiated stimulation may be used in the present invention. Acranial nerve stimulation system may include a sensing lead coupled atits proximal end to a header along with a stimulation lead and electrodeassemblies. A sensor may be coupled to the distal end of the sensinglead. The sensor may include a cardiac cycle sensor. The sensor may alsoinclude a nerve sensor for sensing activity on a nerve, such as acranial nerve, such as the vagus nerve 127.

In one embodiment, the sensor may sense a body parameter thatcorresponds to a symptom of a medical condition. If the sensor is to beused to detect a symptom of the medical condition, a signal analysiscircuit may be incorporated into the IMD 100 for processing andanalyzing signals from the sensor. Upon detection of the symptom of themedical condition, the processed digital signal may be supplied to amicroprocessor in the IMD 100 to trigger application of the electricalsignal to the cranial nerve, such as vagus nerve 127. In anotherembodiment, the detection of a symptom of interest may trigger astimulation program including different stimulation parameters from apassive stimulation program. This may entail providing a higher currentstimulation signal or providing a higher ratio of on-time to off-time.

Turning now to FIG. 5, a flowchart depiction of a method for treating amedical condition, in accordance with one illustrative embodiment of thepresent invention is provided. An electrode may be coupled to a portionof a cranial nerve to enhance cranial nerve evoked potentials. In oneembodiment, one or more electrodes may be positioned in electricalcontact or proximate to a portion of the cranial nerve to deliver astimulation signal to the portion of the cranial nerve (block 710). Theelectrodes may be operatively coupled to at least one of a main trunk ofthe right or left vagus nerve, or any branch thereof. The IMD 100 maythen generate a controlled electrical signal characterized by aninterburst period, a number of pulses per microburst, an interpulseinterval, and a microburst duration, wherein at least one of theinterburst period, the number of pulses per microburst, the interpulseinterval, or the microburst duration is selected to enhance cranialnerve evoked potentials (block 720). This may include a predeterminedelectrical signal that is preprogrammed based upon a particularcondition of a patient. For example, a physician may pre-program thetype of stimulation to provide in order to enhance cranial nerve evokedpotentials in the patient based upon data specific to the patient. TheIMD 100 may then generate a signal, such as a controlled-currentmicroburst signal, to affect one or more portions of the neurologicalsystem of a patient.

The IMD 100 may then deliver the stimulation signal to the portion ofthe cranial nerve (block 730). The application of the electrical signalmay be delivered to the main trunk of the right or left vagus nerve, orany branch thereof. In one embodiment, application of the stimulationsignal may be designed to promote an afferent effect. Further, thestimulation by the IMD 100 may reduce incidents or symptoms relating toa medical condition.

Additional functions, such as a detection process, may be alternativelyemployed with the embodiment of the present invention. The detectionprocess may be employed such that an external detection or an internaldetection of a bodily function may be used to adjust the operation ofthe IMD 100.

Turning now to FIG. 6, a block diagram depiction of a method inaccordance with an alternative embodiment of the present invention isillustrated. The IMD 100 may perform a database detection process (block810). The detection process may encompass detecting a variety of typesof vital signs or other body parameters of the patient. A more detaileddepiction of the steps for performing the detection process is providedin FIG. 7, and accompanying description below. Upon performing thedetection process, the IMD 100 may determine if stimulation is indicated(block 820). Upon a determination that stimulation is not indicated, thedetection process is continued (block 830).

Upon a determination that stimulation is indicated, a determination asto the type of stimulation based upon data relating to the patient'scondition is made (block 840). The type of stimulation may be determinedin a variety of manners, such as performing a look-up in a look-up tablethat may be stored in the memory 217. Alternatively, the type ofstimulation may be determined by an input from an external source, suchas the external unit 270 or an input from the patient. Further,determination of the type of stimulation may also include determiningthe location as to where the stimulation is to be delivered.Accordingly, the selection of particular electrodes, which may be usedto deliver the stimulation signal, is made.

Upon determining the type of stimulation to be delivered, the IMD 100performs the stimulation by delivering the electrical signal to one ormore selected electrodes (block 850). Upon delivery of the stimulation,the IMD 100 may monitor, store, or compute the results of thestimulation (block 860). For example, based upon the calculation, adetermination may be made that adjustment(s) to the type of signal to bedelivered for stimulation, may be performed. Further, the calculationsmay reflect the need to deliver additional stimulation. Additionally,data relating to the results of stimulation may be stored in memory 217for later extraction or further analysis. Also, in one embodiment, realtime or near real time communications may be provided to communicate thestimulation result or the stimulation log to an external unit 270.

Turning now to FIG. 7, a more detailed block diagram depiction of thestep of performing the detection process of block 810 in FIG. 6, isillustrated. The system 100 may monitor one or more vital signs or otherbodily parameters of the patient (block 910). This detection may be madeby sensors residing inside the human body, which may be operativelycoupled to the IMD 100. In another embodiment, these factors may beperformed by external means and may be provided to the IMD 100 by anexternal device via the communication unit 260. In one embodiment, thesensors include a strain gauge that may be used to determine inspirationby identifying chest expansion. By detecting the onset of chestexpansion, the strain gauge may detect the onset of inspiration. Thestrain gauge may also detect expiration by identifying when the chest iscontracting.

Upon acquisition of various signals, a comparison may be performedcomparing the data relating to the signals to predetermined, stored data(block 920). Based upon the comparison of the collected data withtheoretical or stored thresholds, the IMD) 100 may determine whether anappropriate time to commence an on-time block has been reached (block930). Based upon the determination described in FIG. 7, the IMD 100 maycontinue to determine whether further stimulation is indicated, asdescribed in FIG. 6.

Additionally, external devices may perform such calculations andcommunicate the results or accompanying instructions to the IMD 100. TheIMD 100 may also determine the specific location or branch of the nerveto stimulate. The IMD 100 may also indicate the type of stimulation tobe delivered. For example, a microburst electrical signal alone or incombination with another type of treatment may be provided based uponthe quantifiable parameter(s) that are detected. For example, adetermination may be made that a microburst electrical signal by itselfis to be delivered. Alternatively, based upon a particular type ofmedical condition, a determination may be made that a microburstelectrical signal, in combination with a conventional therapeutic VNSsignal, is desirable as a therapy for the patient.

All of the methods and apparatuses disclosed and claimed herein may bemade and executed without undue experimentation in light of the presentdisclosure. While the methods and apparatus of this invention have beendescribed in terms of particular embodiments, it will be apparent tothose skilled in the art that variations may be applied to the methodsand apparatus and in the steps, or in the sequence of steps, of themethod described herein without departing from the concept, spirit, andscope of the invention, as defined by the appended claims. It should beespecially apparent that the principles of the invention may be appliedto selected cranial nerves other than, or in addition to, the vagusnerve to achieve particular results in treating patients havingepilepsy, depression, or other medical conditions.

The particular embodiments disclosed above are illustrative only as theinvention may be modified and practiced in different but equivalentmanners apparent to those skilled in the art having the benefit of theteachings herein. Furthermore, no limitations are intended to thedetails of construction or design herein shown other than as describedin the claims below. It is, therefore, evident that the particularembodiments disclosed above may be altered or modified and all suchvariations are considered within the scope and spirit of the invention.Accordingly, the protection sought herein is as set forth in the claimsbelow.

1-20. (canceled)
 21. A method of treating congestive heart failure usingan implantable medical device (IMD), the method comprising: applying afirst electrical signal during a first stimulation period and applying asecond electrical signal during a second stimulation period to a cranialnerve, wherein: the first electrical signal comprises: a first pulsefrequency; a first pulse width; and a first pulse amplitude; and thesecond electrical signal comprises: a plurality of microbursts appliedat a first microburst frequency, wherein a microburst comprises aplurality of microburst pulses applied during first microburst duration,wherein each microburst pulse comprises: a second pulse width; a secondpulse shape; and a second pulse amplitude.
 22. The method of claim 21,wherein the first stimulation period and the second stimulation periodare each a period of time.
 23. The method of claim 21, wherein the firststimulation period comprises a predetermined number of pulses.
 24. Themethod of claim 21, wherein the second stimulation comprises apredetermined number of microbursts.
 25. The method of claim 21, whereinthe first stimulation period and second stimulation period overlap. 26.The method of claim 21, wherein the first stimulation period or thesecond stimulation period is triggered responsive to a triggering event.27. The method of claim 21, wherein each microburst comprises between 2and 15 microburst pulses and the microburst duration is from 10 msec to80 msec.
 28. The method of claim 21, wherein the cranial nerve isselected from: a vagus nerve; a trigeminal nerve; and a glossopharyngealnerve.
 29. An implantable medical device (IMD) for treating congestiveheart failure, the IMD comprising: a controller, wherein the controllercomprises a processor and a memory; a power supply; and a stimulationunit, wherein the stimulation unit applies a first electrical signalduring a first stimulation period and applies a second electrical signalduring a second stimulation period to a cranial nerve, wherein: thefirst electrical signal comprises: a first pulse frequency; a firstpulse width; a first pulse shape; and a first pulse amplitude; and thesecond electrical signal comprises: a plurality of microbursts appliedat a first microburst frequency, wherein a microburst comprises aplurality of microburst pulses applied during first microburst duration,wherein each microburst pulse comprises: a second pulse width; a secondpulse shape; and a second pulse amplitude.
 30. The implantable medicaldevice (IMD) of claim 29, wherein the first stimulation period and thesecond stimulation period are each a period of time.
 31. The implantablemedical device (IMD) of claim 29, wherein the first stimulation periodcomprises a predetermined number of pulses.
 32. The implantable medicaldevice (IMD) of claim 29, wherein the second stimulation comprises apredetermined number of microbursts.
 33. The implantable medical device(IMD) of claim 29, wherein the first stimulation period and secondstimulation period overlap.
 34. The implantable medical device (IMD) ofclaim 29, further comprising a detection unit, wherein the firststimulation period or the second stimulation period is triggeredresponsive to the detection unit detecting a triggering event.
 35. Theimplantable medical device (IMD) of claim 29, wherein each microburstcomprises between 2 and 15 microburst pulses and the microburst durationis from 10 msec to 80 msec.
 36. The implantable medical device (IMD) ofclaim 29, wherein the cranial nerve is selected from: a vagus nerve; atrigeminal nerve; and a glossopharyngeal nerve.